Recent Advances in the Pathogenesis of Syndromic Autisms

Table 1

Diagnosis and potential therapeutic approaches in some metabolic diseases associated with autism.

Metabolic diseases	Potential patogenetic mechanisms	Clinical features	Diagnosis	Therapetic options	Refs
Phenylketonuria	Low production of dopamine and serotonin. Toxic effects on the brain cells. Reduction of myelin.	Neonatal onset Autism, seizures, severe mental retardation, hyperactivity, EEG abnormalities and seizures, microcephaly, albinism (excessively fair hair and skin) or a tendency to hypopigmentation and eczema, “musty or mousy” odor of skin, hair, sweat, and urine.	Quantitative plasma amino acids analysis. Dosage of phenylpyruvic acid in urine.	Restricted diet + aminoacids administration.	[28, 29]
Adenylosuccinase deficit	Toxic effects of the accumulating succinyl purines on the brain.	Onset in the first year. Autistic phenotype, profound psychomotor retardation, epilepsy, hypotonia, peripheral hypertonia, failure to thrive. No dismorphic features.	Succinyl aminoimidazole, carboxamide riboside and succinyl adenosine in urine and cerebrospinal fluid.	Therapy with D-ribose.	[7, 30]
Smith-Lemli-Opitz syndrome	Neurosteroid deficiency. Alteration of neuroendocrine functions and disruption of the growth and development of many body systems.	Onset in infancy. Autism, mental retardation, sensory hyperreactivity, irritability, language impairment, sleep cycle disturbance, self-injurious behavior, microchepaly, hypotonia, syndactyly, hypogenitalism, malformations of the brain, lung, heart, and gastrointestinal tract.	Abnormal sterol pattern (low plasma and tissue cholesterol concentrations, and increased plasma and tissue 7-dehydrocholesterol reductase and its metabolite).	Cholesterol replacement therapy.	[31, 32]
Creatine deficiency syndromes	Neurotoxic effect of guanidinoacetate or other guanidine compounds.	Autistic phenotype, mental retardation, speech delay, epilepsy, extrapyramidal symptoms, progressive encephalopathy with muscular hypotonia, dyskinetic movements, developmental arrest/regression.	Blood and urinary concentration on creatine and guanidinoacetate, Brain magnetic resonance spectroscopy.	Oral creatine supplementation. Restriction of arginine and substitution of ornithine.	[33]